Project Summary The overarching goal of this project is to use MRI guidance of cardiac resynchronization therapy (CRT) to improve outcomes for heart failure patients selected to undergo this procedure. The importance of using advanced cardiac imaging to make CRT more effective is highlighted by the following statistics: at least 5 million people in the United States have heart failure, 2.5 million require hospitalization, and more than 500,000 are diagnosed with heart failure each year. As a result, this research is highly aligned with the mission of the National Heart, Lung, and Blood Institute to enhance the health of individuals with heart disease or at risk for heart disease so they can live longer and more fulfilling lives. Over the past decade, CRT has emerged as a highly beneficial treatment for many patients with heart failure. CRT involves implantation of an advanced pacemaker/defibrillator attached to three wires in the heart designed to make unevenly pumping hearts contract more synchronously and effectively. Unfortunately, 35-50% of patients do not have improved heart function after CRT, often because of suboptimal positioning of the pacing wires with respect to scar and mechanical activation. In this regard, we have previously demonstrated how MRI strain imaging with the DENSE (Displacement Encoding with Stimulated Echoes) method and contrast-enhanced MRI assessment of scar and coronary veins in the heart can identify the optimal location of the left ventricular CRT pacing site relative to scar and mechanical activation. As a result, there is clinical equipoise for a systematic evaluation with a randomized clinical trial of CRT guided by cardiac MRI for assessment of mechanical activation, scar, and coronary vein anatomy in the heart in order to improve outcomes after CRT. We will randomize 105 patients in a 1:1 ratio, and the primary endpoint will be improvement of left ventricular function as measured by the percent reduction in the left ventricular end systolic volume 6 months after CRT implantation. In the project, we will further refine DENSE strain imaging by improving both three-dimensional and multislice two-dimensional imaging during free breathing by employing imaging-based and projection-based ?navigators.? This is very important because breathing during conventional imaging leads to artifacts in the images, and a significant number of patients with heart disease and heart failure have difficulty holding their breath. In addition, there are an increasing number of CRT pacing settings, and the project also addresses an unmet need for evaluation of the optimal CRT pacing strategy using reproducible assessments of cardiac functional improvement with cardiac MRI to complement echocardiographic assessments. In addition to the application of these methods in CRT, we also emphasize that the improved MRI methods have potential far- reaching applications for other patients with myocardial infarction, valvular heart disease, congenital heart disease, and other types of heart disease. 1